Age-related changes in many physiological parameters have long been known to occur. The basis for these alterations is, however, not well understood. Response to various stresses seems to decline with age. Changes in the ability to metabolize exogenous as well as endogenous compounds has been suggested as a cause for altered functions. This work will explore senescent changes in metabolism of several tissues - liver, lung, kidney, brain, lymphoid tissues. Enzyme systems such as glucuronyl transferase, beta-glucuronidase, prostaglandin synthetase, those involved in glucose and heme metabolism, and those involved in intermediary metabolism and immune responses will be investigated. Altered disposition of chemicals in aging animals is being studied in order to elucidate the basis for age-related changes in pharmacological responses.